The proposed research is directed at continuing our studies aimed at generating cytotoxic lymphocytes in vitro, capable of lysing autologous human leukemia and lymphoma cells. Attempts will be made to generate cytotoxic T lymphocytes (CTLs) mixed leukocyte cultures (MLCs) by culturing remisson T cells with: a) x-irradiated autologous leukemia cells and x-irradiated allogeneic stimulating cells in "three-cell" protocols, or with b) x-irradiated lymphocytes pooled from 20 unrelated normal individuals. The addition to these MLCs, of T cell growth factor (TCGF), highly purified human fibroblast interferon (HFIF) or polyribonucleotide inducers of interferon (IF)may augment the generation of CTLs to autologous malignant cells since these agents markedly enhance the generation of CTLs to alloantigens. A main goal of this research will be to generate large numbers of CTLs cytotoxic for autologous malignant cells; thus, continuous cultures of CTLs, cytotoxic for autologous malignant cells, will be established in TCGF. Further, we propose to isolate clones of CTLs cytotoxic for analogous malignant cells and to use these monoclonal CTSs to determine whether maignant cells from different patients express common target antigens for CTLs. As a correlate to the in vitro human studies, mouse AKR CTLs grown in TCGF, will be tested for their ability to prolong survival of AKR leukemic mice following chemoradiotherapy. HFIF, polyinosinic: polycytidylic acid (poly I:C) and analogues of poly I:C (that differ in their ability to induce IF and cause toxic effects) that augmnt human natural killer (NK) cell activity against leukemia cell lines will be tested for their ability to activate NK cells cytotoxic for fresh autologous leukemia and lymphoma cells. Poly I:C and nontoxic analogues of poly I:C will also be tested in mice for their ability to activate NK cells cytotoxic for syngeneic leukemia cells and for their ability to prolong survival of AKR leukemic mice.